PROJECT ABSTRACT Worldwide, there are ~2.1 million HIV-infected children <15 years old with over 90% living in sub-Saharan Africa (SSA). Cancer risk in youth living with HIV/AIDS (YLWHIV) is markedly increased relative to HIV negative youth and pediatric cancer survival is low in SSA. Cancer studies in YLWHIV in SSA are rare with only one large scale South African study reported to date. In Uganda, where this study will take place, there are no prevalence data available for pediatric cancer among YLWHIV. In response to PAR-18-018, and in line with the current HIV comorbidities priority area at the National Institutes of Health, the goal for the proposed R21 study is to tailor and explore the short-term preliminary outcomes of an existing evidence-based Economic Empowerment (EE) Intervention, Suubi (hope in Luganda -local Ugandan language), on access to pediatric cancer diagnosis, care, and treatment adherence in CLWHIV with suspected cancers. The study will enhance the Suubi EE intervention, titled Suubi4Cancer, through incorporation of cancer education addressing cultural misconceptions regarding cancer tumors. In the proposed Suubi4Cancer study, we will test the theory that youth and their families? cognitive and behavioral change is influenced by economic stability. In addition, we will examine if enhanced cancer knowledge through intra-familial support and communication will help maintain positive behavioral health functioning and reinforce engagement in care and treatment. Suubi4Cancer will leverage a 5-year NIH-funded R01 clinical trial of perinatally HIV-infected children in 39 Ugandan health clinics to collect pilot data needed to explore acceptability and short-term preliminary outcomes of the enhanced intervention. Using medical records (MRs), we will recruit at least 78 youth (ages 10-21) years with suspected malignancies from ~3000 HIV+ youth receiving care in 39 clinics (~ 2 youth/clinic over a 6 month period). We propose three specific aims: Aim 1. Identify confirmed and suspected cancer cases in a cohort of >3000 HIV+ youth (ages 10-21) seen at 39 clinics in 5 districts heavily affected by HIV/AIDS in southern Uganda; Aim 2. Enhance the Suubi EE intervention by including a component addressing misconceptions regarding cancer and explore the acceptability and preliminary impact of Suubi4Cancer on short-term outcomes; and Aim 3. Explore multi-level factors (individual, family, cultural) impacting participants? participation in and experiences with the Suubi4Cancer. Our study findings will contribute to: 1) the initiation of a regional registry for YLWHIV for cancer research; and 2) our understanding of the short-term impact of combination interventions addressing access to cancer diagnosis, care, and treatment adherence among YLWHIV in SSA. The study will advance knowledge about pediatric cancer in the context of HIV infection and will inform the design of an R01 study allowing for better understanding of the role of combination interventions in addressing low pediatric cancer survival rates in YLWHIV and potentially all youth in SSA.